Potassium Carbonate → HCID 16037392, compound

HRID 1806269Notes

Reaction equation

HRID 1806269 reaction equation
[CH3:1][CH:2]([NH:6][CH2:7][C:8]1[S:12][C:11](B(O)O)=[CH:10][CH:9]=1)[CH2:3][O:4][CH3:5].Br[C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([C:26]([NH2:28])=[O:27])[CH:25]=1)[NH:22][CH:21]=[C:20]2[CH:29]1[CH2:34][CH2:33][N:32]([S:35]([CH2:38][CH3:39])(=[O:37])=[O:36])[CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.O.O1CCOCC1>[CH2:38]([S:35]([N:32]1[CH2:31][CH2:30][CH:29]([C:20]2[C:19]3[C:23](=[C:24]([C:26]([NH2:28])=[O:27])[CH:25]=[C:17]([C:11]4[S:12][C:8]([CH2:7][NH:6][CH:2]([CH3:1])[CH2:3][O:4][CH3:5])=[CH:9][CH:10]=4)[CH:18]=3)[NH:22][CH:21]=2)[CH2:34][CH2:33]1)(=[O:37])=[O:36])[CH3:39]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 113844275-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamideHCID 66723103HCID 66723103, compound

Product 1

HCID 16037392HCID 16037392, compoundYield 35.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

[5-({[1-methyl-2-(methyloxy)ethyl]amino}methyl)-2-thienyl]boronic acid (60 mg, 0.262 mmol) was transferred to a CEM microwave tube with methanol. The methanol was evaporated under a stream of N2. To this was added 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (80 mg, 0.19 mmol), potassium carbonate (160 mg, 1.16 mmol), tetrakis(triphenylphosphine)palladium(0) (5 mg, 0.004 mmol), dioxane (1.5 mL), and water (0.5 mL). The vial was capped and reacted in a CEM microwave at 150° C. for 30 min. This solution was loaded onto a 2 g SCX SPE cartridge primed with 3 mL of methanol. The cartridge was then sequentially eluted with water (3 mL), methanol (9 mL), and 2M NH3 in MeOH (6 mL). The NH3 in MeOH fractions were dried under a stream of N2 at 40° C. The crude product was taken up in dimethyl sulfoxide (1 mL) and purified on an Agilent MDAP with UV (230 nm) and MS detection. The desired fractions were passed thru two sequential 500 mg Pharmasil CHQAX cartridge primed with 1 mL of methanol and 1 mL of water. The solvents were evaporated under a stream of N2 at 60° C. to give 34.7 mg of the title compound (34%).

Workup

  1. customThe methanol was evaporated under a stream of N2
  2. customThe vial was capped
  3. customreacted in a CEM microwave at 150° C. for 30 min
  4. washThe cartridge was then sequentially eluted with water (3 mL), methanol (9 mL), and 2M NH3 in MeOH (6 mL)
  5. dry with materialThe NH3 in MeOH fractions were dried under a stream of N2 at 40° C
  6. custompurified on an Agilent MDAP with UV (230 nm) and MS detection
  7. customThe solvents were evaporated under a stream of N2 at 60° C.

Sources & evidence

ORD record
ord-8a5084c70bd94819b8abf4c2a0925290
Source dataset
uspto-grants-2013_01
Patent number
US08354406B2

Reaction notes

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